June 7, 2007

Kirby on HuffPo: See You In (Vaccine) Court

On Monday, one of the most important legal proceedings in American medical history will get underway at the U.S. Court of Federal Claims in Washington. There, a special panel of three judges will begin hearing evidence to support -- and refute -- the hypothesis that mercury in vaccines and/or the live-virus measles-mumps-rubella shot caused autism or autism-like symptoms in some American children.

Monday will mark the first time ever that evidence of autistic harm from childhood vaccines is examined and cross-examined in a court of law. This is far from a slam dunk case for either side, and the stakes - professional, financial, emotional - could not be more intense.

These three judges from the federal "Vaccine Court," as it is called, are about to dip into the raging, contradictory waters of the vaccine-autism contretemps, knowing they must emerge on the other side, each with their own acutely anticipated decision about causation. Ultimately, they must deliver judgment on some 4,800 claims that have been languishing in the system for years.

I do not envy them their task.

Technically, at least, this is not a trial at all; it is an "Autism Omnibus Proceeding" in a no-fault, supposedly non-adversarial adjudication. The judges are not judges, but "Special Masters;" plaintiff families and their lawyers are called "petitioners," and the defendant, called the "respondent," is not some drug giant, but the Department of Health and Human Services, represented by well-funded attorneys at the US Justice Department.

Any claims awarded in Vaccine Court are paid from a 75-cents-per-vaccine tax footed by consumers, leaving vaccine makers free from liability.

But if even one case of causation is determined, then private lawsuits in civil courts - where the drug makers themselves are on trial - would soon flood the dockets. (Ironically, if families lose in Vaccine Court, they are free to sue in civil court. Having autistic kids appear before sympathetic juries is Big Pharma's big nightmare, and it's why a secret rider was attached to the Homeland Security Act of 2002 to bar thimerosal cases from civil court and force them into Vaccine Court).

Over the next three weeks, evidence on both sides of the first "test case" will be picked apart to its bare bones, with one gaping exception. Petitioners were just denied access to the government's vast vaccine safety database of HMO patients, which was used by CDC officials to conduct a four-year study that ultimately found no link between thimerosal and autism. Earlier versions of the study, obtained through the Freedom of Information Act, however, clearly showed increased risks for many neurodevelopmental disorders, depending on the dose of thimerosal administered.

No wonder a special panel convened by the NIH recently issued a harsh critique of the CDC's data collection and management, saying the study contained "several serious problems... weaknesses and limitations" that "reduce its usefulness" in proving or disproving causation.

And so, numbers culled from the government's massive database will be submitted as Exhibit A for the defense, though the other side will be forever barred from seeing the actual raw data, in order to replicate what the CDC researchers found. (Exact replication is impossible because original datasets, culled at taxpayer expense, somehow "went missing" and are no longer available for re-analysis - a possible felony violation of the federal Data Quality Act).

On the other hand, the burden of proof for plaintiffs is lower in Vaccine Court than other federal courts, which could even things out a little.

Nearly all of the government's evidence will be "epidemiological" in nature - based on large population studies of computerized data. These include the CDC study, plus similar research done in Sweden, Denmark and the UK which found that, if anything, thimerosal had a "neuro-protective" effect on children by apparently reducing their risk of autism.

Petitioning attorneys will counter that Federal Court rules regard epidemiology alone as being "insufficient" to disprove causation, and will surely use the NIH panel's critique of the government's own database as a roadmap toward defanging the CDC's conclusions. To begin with, the CDC found an autism rate of just 11-per-10,000 children at the largest participating HMO, where the actual rate is currently 73-per-10,000. Why so many excluded children, they will likely ask, and how did this affect the rate of outcomes?

As for Denmark, petitioning lawyers will argue that autism case numbers increased after 1992, when thimerosal was removed from childhood vaccines, mostly because the Danish government happened to switch from counting inpatient-diagnosed cases only - about 13% of the total - to counting all inpatient AND outpatient cases nationwide. By 1999 the total number had "gone up" to about 200 children a year, in a nation of 6.2 million people - well below the current US rate of 1-in-150 kids, and not exactly a raging epidemic.

The lawyers might also point out that incidence and prevalence rates of autism actually declined in Denmark during 2000, and again (we now know, only through FOIA) in 2001. And they could cite a media quote from Dr. Irva Hertz-Picciotto, professor of public health at UC-Davis School of Medicine and chair of the NIH panel that critiqued the CDC study. Flawed as the CDC analysis was, she called it "an improvement on other studies, including the two in Denmark, both of which had serious weaknesses in their designs."

For their side of the argument, family lawyers will present thousands of pages of published "biological" science, as opposed to epidemiology. They will examine data from animal models, test tube studies, and examinations of children with autism; they will try to present a plausible biological mechanism by which mercury (and to a lesser extent, MMR) could cause autistic-like symptoms -- at the molecular, cellular, and clinical level.

Among this evidence is research suggesting that:

1) Many children with autism, probably due to genetics, are deficient in certain sulfur-based proteins that defend against heavy metal accumulation in humans. The proteins, which include glutathione, are called "thiols," and sometimes "mercaptans," from the Latin mercurium captans, or literally "mercury capturers."

2) Many children with autism show signs of heavy metal accumulation, including elevated levels of proteins called "prophyrins" a bio-marker of lead and mercury toxicity. They also present with low levels of mercury in baby haircuts, (versus control children) suggesting a heavy metal "efflux disorder" that prevents the proper metabolism and excretion of heavy metals.

3) Exposure to extremely low doses (micromolars) of thimerosal, previously thought to be safe, shut down 25% of brain stem cells, in one lab study.

4) In another, low-level exposures of a few minutes duration killed many of the immune system's "dendritic" cells, disrupted production of immune-system messenger chemicals called "cytokines," and caused inflammation.

5) Meanwhile, many children with autism show signs of immune deficiency AND hyperactivity, as well as cytokine imbalances and inflammation, (they also show signs of chronic autoimmunity, where the immune system attacks the body and brain).

6) Organic ethylmercury from thimerosal crosses the blood-brain barrier in primates, where it quickly converts to inorganic mercury, which can remain trapped in the brain for decades.

8) Autopsies on autistic human brains found chronic inflammation, apparently linked to the brain's immune system and produced by activation of its "glial" cells.

9) Another autopsy study also showed ongoing neuro-inflammation, possibly from heavy metal exposure, and signs of autoimmunity. (Other studies have found rapid brain growth in infants with autism.)

10) Thimerosal can disrupt a chemical process called "methylation," critical for gene expression, neural function, memory and attention, and the production of sulfur-based "thiol" proteins like glutathione.

Plaintiff lawyers will also show data from a study of birthday videos proving that many kids with autism were meeting or exceeding developmental milestones at age one, only to have tumbled into a wordless, autistic world by age two. They will also show home videos of plaintiff children, before and after their own regression, and in many cases, of the same children a few years after experimental treatments - including chelation (for heavy metal removal) and methyl B-12 (for repair of methylation) - that seem to have vastly improved their condition.

At this point, government lawyers will surely try to discredit these biological studies, one-by-one. They could succeed, though it will be tough, given the data's provenance. Lead authors come from institutions such as Harvard, Northeastern, Columbia, UC Davis, Johns Hopkins, and the Universities of Washington, Arkansas, Kentucky and Rochester, and their papers were published in peer-reviewed journals such as Molecular Psychiatry, and the NIH's Environmental Health Perspectives.

The defense also has a few biological studies to support its side, including one showing no difference in the mercury levels of blood and hair of typical vs. autistic kids. But the mean age in this study was four years old, and mercury does not linger around in blood or hair for that long.

Another study showed the thimerosal containing drug Rho-Gam (given to pregnant women, and not a vaccine) did not increase the risk of autism in children, though this study was funded by Johnson & Johnson, the product's manufacturer and a potential thimerosal litigation defendant.

Likewise, the plaintiffs might offer some epidemiology, including one study from the University of Texas showing increased rates of autism in school districts near mercury-emitting coal power plants, and another, funded by the CDC itself, where children with autism in the SF Bay Area were 50% more likely to be born in the region's most mercury-polluted tracts, suggesting "a potential association between autism and estimated metal concentrations."

Finally, expect to hear hours of testimony about California. Mercury was phased out of childhood vaccines (except the flu shot) a few years ago, the argument goes, so there should have been a drop in autism rates by now, especially in California, which keeps the most reliable autism statistics. It's a very powerful contention, but it may be too early to make any final conclusions.

Among the youngest children, 3-to-5-year-olds, the number of cases was still increasing after the first quarter of 2007. These kids were born and vaccinated between 2002 and 2004, after thimerosal was removed from vaccines, right?

It's true, most companies started making preservative-free vaccine in 2001, but they also continued making product with thimerosal, as a backup during the transition period. Little, if any of those mercury-containing vaccines were ever recalled: They remained on the market, until they were finally used up or expired, in 2003.

Government lawyers will likely point to a 2002 survey of vaccine providers, conducted by the CDC, showing that just 2% of the pediatric shots contained thimerosal. But this was a survey of providers under CDC contract only, and CDC had a record of buying mercury-free vaccines for its clients (ie, state, county and other public health clinics) even before 1999, when the federal government called for the removal of thimerosal from the pediatric schedule "as soon as possible."

It's not clear how many of the CDC contract providers surveyed were in California, where the vast majority of children receive care in private practices and large HMOs. Moreover, the CDC survey was merely a "convenience sample," which are so inaccurate in representing the general population they are virtually never used in published data. In fact, the US DOJ itself defines them as "rarely useful in evaluation and usually hazardous."

Meanwhile, the state has quietly been tracking the number of autism cases by birth year, as well as age group, meaning we can look at the very youngest children entering the system. In the first quarter of 2003, there were 170 children with autism in the state system born in 2000 (or, roughly, three-year-olds). In the first quarter of 2004, the number of three-year-olds increased 8.2% to 184. In 2005 the same number went up 13%, to 208, and in 2006 it jumped nearly 27% to 264. But this year, among kids born in 2004, it was 251, a 5% drop.

This could be attributable to some quarterly reporting glitch, and the caseload could easily be made up in the next quarter (that data will be out in mid-July). But if the deficit continues, the 2004 birth cohort could finish out as the first in which case numbers actually fell. (A similar trend might be emerging at Northern California Kaiser, a major HMO).

Of course, it would take tremendous resources to get to the bottom of this, lawyers might argue. One would need full medical records on each of those 251 kids born in 2004. Did any receive thimerosal still left in California vaccines (or prenatally via Rho-Gam)? How many were exposed to mercury in flu shots during pregnancy and as infants? And in a population that is now one-quarter foreign born, how many children immigrated from countries where immunization with thimerosal is now routine? (Vaccination coverage in Mexico is now 92%).

Is immigration helping keep the California numbers up? We don't have that data. But we do know that, since 2003, the rate of increase among white and black children was 48.6% and 51.6%, respectively. Among Asian children, however, it was 79%, and among Hispanics, 84.2%. Probably something worth looking into (as well as the effect of aggressive early intervention campaigns, which have consistently brought down the average age of diagnosis and would likely drive up the number of three year olds in the system).

But again, this is epidemiology coming out of California, and the Special Masters are looking at specific children with specific claims before their court. Officials from the state have been warning all of us (and that includes me) not to read too much into these numbers.

At the International Meeting For Autism Research last month, California health officials presented their data along with this caveat: "Limitations of the database and lack of individual exposure data prevent conclusions, based on these data, about thimerosal as a cause or modifier of autism in a specific subgroup or child."

It is entirely possible that thimerosal itself did not cause the autism epidemic, but that is not what is on trial here. Even so, for the sake of argument, let's say that a "specific subgroup" of people with autism, maybe 1%, was affected by mercury in their vaccines. With an estimated 1.5 million Americans with autism, that would mean 15,000 people severely impacted by thimerosal.

But, if causation can be shown in even 1% of cases, this would provide tremendous hope for the other 99%. Yes, some cases may be purely genetic in nature. But for everyone else, if we can show how thimerosal caused "autism," we might be able to do the same for, say, pesticides, PCBs, flame retardants, jet fuel, environmental mercury in air, water and fish, or any combination thereof.

It's a tough call and, like I said, I don't envy these Special Masters, though I do thank them for opening the proceedings to the public.

And I will see you in Vaccine Court.

----------------

David Kirby is author of the book "Evidence of Harm." Many of the studies cited here can be found on his Powerpoint slides at www.evidenceofharm.com